{"id":152,"date":"2021-12-06T12:16:59","date_gmt":"2021-12-06T11:16:59","guid":{"rendered":"http:\/\/wordpress.p604513.webspaceconfig.de\/research\/projektbereich-c\/"},"modified":"2023-11-07T12:16:27","modified_gmt":"2023-11-07T11:16:27","slug":"project-area-c","status":"publish","type":"page","link":"https:\/\/www.loewe-druid.de\/en\/research\/project-area-c\/","title":{"rendered":"Project area C"},"content":{"rendered":"\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-1c44u-3b6089b1101e1de254658a9d832c4345\">\n.flex_column.av-1c44u-3b6089b1101e1de254658a9d832c4345{\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div  class='flex_column av-1c44u-3b6089b1101e1de254658a9d832c4345 av_one_fourth  avia-builder-el-0  el_before_av_three_fourth  avia-builder-el-first  rahmen-headline-projects first flex_column_div av-zero-column-padding avia-link-column av-column-link avia-link-column-hover  '    data-link-column-url=\"https:\/\/www.loewe-druid.de\/forschung\/projektbereich-e\/\"   ><a class=\"av-screen-reader-only\" href=https:\/\/www.loewe-druid.de\/forschung\/projektbereich-e\/ >Link to: Projektbereich E<\/a><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-kzfmava6-7a741416da99901c159bce0f687ecd81\">\n#top .av-special-heading.av-kzfmava6-7a741416da99901c159bce0f687ecd81{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-kzfmava6-7a741416da99901c159bce0f687ecd81 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-kzfmava6-7a741416da99901c159bce0f687ecd81 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-kzfmava6-7a741416da99901c159bce0f687ecd81 av-special-heading-h1 blockquote modern-quote  avia-builder-el-1  avia-builder-el-no-sibling '><h1 class='av-special-heading-tag '  itemprop=\"headline\"  >Project area C:<\/h1><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-45q6-0f076e3af53f8a7bf974ecb575e38d59\">\n.flex_column.av-45q6-0f076e3af53f8a7bf974ecb575e38d59{\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div  class='flex_column av-45q6-0f076e3af53f8a7bf974ecb575e38d59 av_three_fourth  avia-builder-el-2  el_after_av_one_fourth  avia-builder-el-last  rahmen-accordion-projects border-left flex_column_div av-zero-column-padding  '     ><div class=\"togglecontainer toggle_close_all  avia-builder-el-5  avia-builder-el-no-sibling  enable_toggles projekte_toggle\"><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C1<\/span><span class=\"project_title\">Targets for antiviral strategies against ZIKV<\/span><br><span class=\"project_names\">Daniela Bender, Eberhard Hildt<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/daniela-bender.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/daniela-bender.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Dr. Daniela Bender<\/strong><\/p><p><p>Paul-Ehrlich-Institut<br \/>\nBundesinstitut f\u00fcr Impfstoffe<br \/>\nund biomedizinische Arzneimittel<br \/>\nPaul-Ehrlich-Stra\u00dfe 51-59<br \/>\n63225 Langen<br \/>\nTel.: +49 (0)6103-77 5411<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:Daniela.Bender@pei.de\">Daniela.Bender(at)pei(dot)de<\/a><\/p>\n<p><a href=\"http:\/\/www.pei.de\/DE\/forschung\/forschungsgruppen\/virologie\/virologie-node\" target=\"_blank\" rel=\"noopener\">Homepage<\/a><\/p>\n<\/p><\/div><hr><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/eberhard-hildt.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/eberhard-hildt.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Eberhard Hildt<\/strong><\/p><p><p>Bundesinstitut f\u00fcr Impfstoffe<br \/>\nund biomedizinische Arzneimittel<br \/>\nPaul-Ehrlich-Institut<br \/>\nPaul-Ehrlich-Stra\u00dfe 51-59<br \/>\n63225 Langen<br \/>\nTel.: +49 (0)6103-77 2140<br \/>\nFax: +49 (0)6103-77 1234<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:Eberhard.Hildt@pei.de\">Eberhard.Hildt(at)pei(dot)de<\/a><\/p>\n<p><a href=\"http:\/\/www.pei.de\/DE\/forschung\/forschungsgruppen\/virologie\/virologie-node\" target=\"_blank\" rel=\"noopener\">Homepage<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description:<\/strong><\/p>\n<p>Zika viruses (ZIKV) are arboviruses, which belong to the <em>flaviviridae<\/em> family. During the ZIKV outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. The WHO declared a public health emergency of international concern (PHEIC). At present neither a preventive vaccine or antiviral drugs are available. By inhibition of virus replication in an early phase of the viral life cycle if applicable as a temporary preventive approach, the viral load could be significantly reduced.\u00a0 Thereby, the spread of the virus would be impaired and the risk of an intrauterine infection would be reduced.\u00a0 During the first funding period target structures could be identified.<\/p>\n<div id=\"attachment_542\" style=\"width: 699px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-542\" class=\"wp-image-542 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c01-grafik-01.png\" alt=\"\" width=\"689\" height=\"350\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c01-grafik-01.png 689w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c01-grafik-01-300x152.png 300w\" sizes=\"auto, (max-width: 689px) 100vw, 689px\" \/><p id=\"caption-attachment-542\" class=\"wp-caption-text\">Intracellular distribution of tetherin (red) and ZIKV envelope protein (green) in cells that were infected either by the Uganda or the French Polynesia isolate.<\/p><\/div>\n<p><strong>Scientific goal: <\/strong><\/p>\n<p>Based on already identified targets and further targets, antiviral strategies are developed, the underlying mechanisms will be investigated and the effect on additional members of the <em>flaviviridae<\/em> family will be studied.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A2 Gr\u00fcnweller lab, B1 Diderich\/Kolb lab, B6P Herker lab, C2 Kempf lab, C5 Glebe\/Geyer lab, D1 Steinmetzer lab, E6 Schiffmann\/Laux lab<\/p>\n<hr \/>\n<p>References C1: <strong>1.\u00a0<\/strong>Herrlein <em>et al.<\/em>\u00a0<strong>(2021)\u00a0<\/strong>J Virol. doi: 10.1128\/jvi.02117-2\u00a0 <strong>2.\u00a0<\/strong>Sabino <em>et al (<strong>2021).<\/strong><\/em><strong>,<\/strong>\u00a0J Virol. doi: 10.1128 <strong>3.<\/strong>\u00a0Maddaluno et al., <strong>2020 <\/strong>EMBO Mol Med. doi: 10.15252\/emmm.201911793 <strong>4.<\/strong>\u00a0Basic <em>et al.<\/em>\u00a0<strong>2019 Antiviral Res. doi: 10.1016\/j.antiviral.2019.104644<\/strong>.\u00a0<strong>5.<\/strong>\u00a0Akhras<em> et al.<\/em>\u00a0<strong>(2019)<\/strong>\u00a0<strong><em>Viruses<\/em><\/strong> doi: 10.3390\/v11080748<em>.<\/em>\u00a0<strong>6<\/strong>.\u00a0 Sabino <em>et al<\/em>., <strong>(2019)<\/strong> doi: 10.3390\/v11060524 <strong>7.<\/strong>\u00a0Elgner et al <strong>(2018)<\/strong>\u00a0<strong><em>Viruses\u00a0<\/em><\/strong><em>doi: 10.3390\/v10040149<\/em><\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C2<\/span><span class=\"project_title\">Bartonella bacilliformis pathogenicity factors as diagnostic and therapeutic targets<\/span><br><span class=\"project_names\">Volkhard Kempf<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/volkhard-kempf.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/volkhard-kempf.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Volkhard A. J. Kempf<\/strong><\/p><p><p>Universit\u00e4tsklinikum Frankfurt<br \/>\nInstitut f\u00fcr Medizinische Mikrobiologie<br \/>\nund Krankenhaushygiene<br \/>\nGoethe-Universit\u00e4t Frankfurt\/Main<br \/>\nPaul-Ehrlich-Str. 40<br \/>\n60596 Frankfurt\/Main<br \/>\nTel.: +49 (0)69-6301 5019<br \/>\nFax: +49 (0)69-6301 83431<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:volkhard.kempf@kgu.de\">volkhard.kempf(at)kgu(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<p><em>Bartonella bacilliformis <\/em>is the causative agent of Carri\u00f3ns disease, a vector borne illness restricted to the South American Andes. The bacteria cause severe hemolytic fever with high fatality rates. The inhibition of hemolysis represents a promising therapeutic approach. Two <strong>pathogenicity factors<\/strong> play a crucial role in hemolysis of which at least one represents a promising drug target. Humans are the only known reservoir host for <em>B. bacilliformis<\/em> and represent the source of new outbreaks. It is therefore of particular importance for disease control to identify asymptomatic carriers. For this, an alpha version of a <strong><em>B. bacilliformis<\/em> IgG ELISA<\/strong> and <strong>line blot <\/strong>were developed.<\/p>\n<div id=\"attachment_302\" style=\"width: 310px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-302\" class=\"wp-image-303 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/projekt-c02-bild01-300x264.png\" alt=\"\" width=\"300\" height=\"264\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c02-bild01-300x264.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c02-bild01.png 442w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-302\" class=\"wp-caption-text\"><em>Scanning electron microscopy of infected human erythrocytes with B. bacilliformis.<\/em><\/p><\/div>\n<div id=\"attachment_304\" style=\"width: 310px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-304\" class=\"wp-image-305 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/projekt-c02-bild02-300x225.png\" alt=\"\" width=\"300\" height=\"225\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c02-bild02-300x225.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c02-bild02.png 471w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-304\" class=\"wp-caption-text\"><em>B. bacilliformis<\/em><em> NovaLisa\u00ae KIT.<\/em><\/p><\/div>\n<p><strong>Scientific goal:<\/strong><\/p>\n<p>The project aims to analyze the role of the two pathogenicity factors in the process of hemolysis to develop a novel, anti-virulence-based therapeutic strategy. Furthermore, the alpha version of the <em>B. bacilliformis<\/em> IgG ELISA and line blot will be evaluated in field studies in cooperation with our partners from Lima\/Peru.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A7 Przyborski lab, C1 Bender \/ Hildt, E7 Locker lab, Gold Standard Diagnostics (formerly NovaTec)<\/p>\n<hr \/>\n<p>References C2: [1] Garcia-Quintanilla <em>et al<\/em>.<strong> (2019) <\/strong><strong><em>Parasites&amp;Vectors<\/em><\/strong> 12(1):141, [2] Riess <em>et al.<\/em> <strong>(2004)<\/strong> <strong><em>J Exp Med <\/em><\/strong>200:1267-78, [3] Dichter <em>et al. <\/em><strong>(2019)<\/strong> <strong><em>Microbiology Res Announc<\/em><\/strong>, DOI: 10.1128\/MRA.01377-19, [4] Dichter <em>et al<\/em>. <strong>(2021)<\/strong> <strong><em>Lancet Microbe<\/em> <\/strong>2:e685\u201394.<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C3<\/span><span class=\"project_title\">Complement-interacting proteins of relapsing fever Borrelia<\/span><br><span class=\"project_names\">Peter Kraiczy<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/peter-kraiczy.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/peter-kraiczy.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Peter Kraiczy<\/strong><\/p><p><p>Goethe-Universit\u00e4t Frankfurt\/Main<br \/>\nInstitut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene<br \/>\nUniversit\u00e4tsklinikum Frankfurt<br \/>\nPaul-Ehrlich-Str. 40<br \/>\n60596 Frankfurt am Main<br \/>\nTel.: +49 (0)69-6301 7165<br \/>\nFax: +49 (0)69-6301 83431<br \/>\nE-Mail <a class=\"mail\" href=\"mailto:kraiczy@em.uni-frankfurt.de\">kraiczy(at)em.uni-frankfurt(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description:<\/strong><\/p>\n<p><em>Borrelia recurrentis<\/em> is considered as a &#8220;<em>neglected arthropod-borne pathogen<\/em>&#8221; and the causative agent of louse-borne relapsing fever. If left untreated, the case-fatality rate of this epidemic disease can exceed &gt;40%. The hematogenous dissemination suggests that borreliae developed efficient immune evasion strategies to overcome innate immunity, in particular complement. Proteins interacting with complement are known to play a crucial role in host-pathogen interaction. Bioinformatic analyses revealed a <strong>cluster of five proteins<\/strong> all of which inhibit complement at different activation levels. Of importance, molecules interacting with the immune system represent promising candidates for the <strong>development of in vitro diagnostics<\/strong>. Two test systems (<strong>Line immunoblot<\/strong> and <strong>ELISA<\/strong>) for the diagnosis of louse-borne relapsing fever have already been developed and evaluated.<\/p>\n<div id=\"attachment_332\" style=\"width: 167px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-332\" class=\"wp-image-333 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild01.jpg\" alt=\"\" width=\"157\" height=\"226\" \/><p id=\"caption-attachment-332\" class=\"wp-caption-text\">Immunofluorescene microscopy of <em>B. recurrentis.<\/em><\/p><\/div>\n<div id=\"attachment_330\" style=\"width: 310px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-330\" class=\"wp-image-331 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/projekt-c03-bild02-300x181.png\" alt=\"\" width=\"300\" height=\"181\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild02-300x181.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild02-1030x620.png 1030w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild02-768x462.png 768w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild02-705x424.png 705w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c03-bild02.png 1274w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-330\" class=\"wp-caption-text\">Schematic representation of the complement inactivation on the outer surface of <em>B. recurrentis.<\/em><\/p><\/div>\n<p><strong>Scientific goal: <\/strong><\/p>\n<p>The focus of this project deals with the functional and structural <strong>characterization of additional complement-inhibiting proteins<\/strong> of <em>Borrelia recurrentis<\/em> as well as the optimization of the evaluated test systems and the development of a <strong>point-of-care antigen test<\/strong> for the diagnosis of relapsing fever.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>B2 Ziebuhr lab, C2 Kempf lab, C4 Steinhoff lab, D1 Steinmetzer lab, E3 Rahlfs\/Przyborski, Gold Standard Diagnostics (formerly NovaTec)<\/p>\n<hr \/>\n<p>References C3: [1] Cordes <em>et al.<\/em> <strong>(2005) <em>Nat Struct Mol Biol <\/em><\/strong>12:276-277; [2] R\u00f6ttgerding <em>et al.<\/em><strong> (2017) <em>Sci Rep<\/em><\/strong> 7:303; [3] Nguyen<em> et al.<\/em><strong> (2018) <\/strong><strong><em>Front Cell Infect Microbiol.<\/em><\/strong> 8:23; [4] Walter<em> et al.<\/em> <strong>(2019) <em>Front Immunol<\/em><\/strong> 10:2722; [5] R\u00f6ttgerding and Kraiczy <strong>(2020) <\/strong><strong><em>Front Immunol<\/em><\/strong> 11:1560; [6] Schmidt et al. <strong>(2021)<\/strong> <strong><em>Sci Rep<\/em><\/strong> 11:4964.<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C4<\/span><span class=\"project_title\">Improved diagnosis and therapy of visceral Leishmaniasis<\/span><br><span class=\"project_names\">Ulrich Steinhoff<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/ulrich-steinhoff.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/ulrich-steinhoff.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Ulrich Steinhoff<\/strong><\/p><p><p>Institut f\u00fcr Medizinische Mikrobiologie und Krankenhaushygiene<br \/>\nPhilipps-Universit\u00e4t Marburg<br \/>\nHans-Meerwein-Stra\u00dfe 2<br \/>\n35043 Marburg<br \/>\nTel.: +49 (0)6421-28 66134<br \/>\nFax: +49 (0)6421-58 66420<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:ulrich.steinhoff@staff.uni-marburg.de\">ulrich.steinhoff(at)staff.uni-marburg(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description:<\/strong><\/p>\n<p>A reliable <strong>diagnosis<\/strong> and treatment of humans and dogs (reservoir host) suffering from visceral leishmaniasis (VL) is crucial for the control of this infection. Currently available diagnostic tests based on the antibody reaction with the Leishmania kinesin protein show poor sensitivity in some endemic areas. We have developed and patented a kinesin antigen (rKLi8.3) with an improved diagnostic performance in humans and animals. This was possible by developing a kinesin antigen with an optimized kinesin structure (repeats) and sequence. Currently various test formats with the rKLi 8.3 antigen are produced and tested with sera from infected humans and dogs.<\/p>\n<p>The <strong>treatment <\/strong>of VL is problematic in terms of effectiveness and side effects. An inhibitor (GNF-6702) that selectively inhibits the proteasome of the Kinetoplastida (<em>T. brucei, T. cruzei and L. donovani<\/em>) has been developed. GNF-6702 binds to a proteasome subunit of Kinetoplastida (beta 4 subunit) that is structurally distinct from humans. The specific bind-ing to the kinetoplast proteasome seems to be the reason for the very low toxicity in mam-malian cells. We could demonstrate that the proteasomal beta 4 subunit is conserved in all Leishmania isolates, tested to date. Thus, the proteasome is a promising therapeutic target.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Scientific goal: <\/strong><\/p>\n<p>In the <strong>diagnostic<\/strong> part of the project, various formats of a sero-diagnostic VL rapid test will be manufactured and tested in cooperation with our industrial partner. In the <strong>treatment<\/strong> part of the project, we validate the specificity, effectiveness and toxicity of the new, kinetoplastid-specific proteasome inhibitors in cell culture experiments of Leishmania infected macrophages.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>B1 Diederich\/Kolb lab, C2 Kempf lab,\u00a0D3 van Zandbergen lab<\/p>\n<hr \/>\n<p>References C4:<strong> [1] <\/strong>Abass <em>et al.<\/em> (2013) <strong>PLoS Negl Trop Dis<\/strong>. 18;7; <strong>[2]<\/strong> Abass <em>et al<\/em>. (2015) <strong>PLoS One<\/strong>. 3;10; <strong>[3]<\/strong> Mart\u00ednez Abad et al. (2017) <strong>Acta Trop<\/strong>. 166:133-138; <strong>[4]<\/strong> Pereira <em>et al.<\/em> (2020) <strong>Eur J Microbiol Immunol<\/strong> 27;10:165-171. <strong>[5] <\/strong>Khare <em>et al<\/em>. (2016) <strong>Nature<\/strong> 537: 229-233<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C5<\/span><span class=\"project_title\">Hit-to-lead development of selective HBV\/HDV entry inhibitors<\/span><br><span class=\"project_names\">Joachim Geyer, Dieter Glebe<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/dieter-glebe.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/dieter-glebe.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Dieter Glebe<\/strong><\/p><p><p>Institut f\u00fcr Medizinische Virologie<br \/>\nJustus-Liebig-Universit\u00e4t Gie\u00dfen<br \/>\nSchubertstra\u00dfe 81<br \/>\n35392 Gie\u00dfen<br \/>\nPhone: +49 (0)641-99 41246<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:dieter.glebe@viro.med.uni-giessen.de\">dieter.glebe(at)viro.med.uni-giessen(dot)de<br \/>\n<\/a><\/p>\n<\/p><\/div><hr><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/joachim-geyer.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/joachim-geyer.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Joachim Geyer<\/strong><\/p><p><p>Institut f\u00fcr Pharmakologie und Toxikologie<br \/>\nJustus-Liebig-Universit\u00e4t Gie\u00dfen<br \/>\nSchubertstra\u00dfe 81<br \/>\n35392 Gie\u00dfen<br \/>\nPhone: +49 (0)641-99 38404<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:joachim.m.geyer@vetmed.uni-giessen.de\">joachim.m.geyer(at)vetmed.uni-giessen(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description:<\/strong><\/p>\n<p>Infections with the Hepatitis B (HBV) and D (HDV) viruses are the main cause of hepatocellular carcinoma and liver cirrhosis as a consequence of chronic hepatitis. Although an effective prophylactic vaccine is available, therapeutic options are highly limited, in particular for HDV. A promising novel drug target to block HBV\/HDV virus entry into hepatocytes is represented by the hepatic bile acid carrier NTCP (Na<sup>+<\/sup>\/taurocholate co-transporting polypeptide) that has been identified as the bona fide hepatic receptor for HBV\/HDV. So far, more than 200 compounds from different compound classes have been tested and corresponding 3D structure-activity-relationship (QSAR) models have been generated. Furthermore, a pharmacophore model for HBV\/HDV entry inhibitors was established. Virtual compound libraries have already been screened with these models and further effective hits have been identified.<\/p>\n<div id=\"attachment_388\" style=\"width: 310px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-388\" class=\"wp-image-388 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/projekt-c05-bild01-300x245.png\" alt=\"\" width=\"300\" height=\"245\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c05-bild01-300x245.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-c05-bild01.png 505w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-388\" class=\"wp-caption-text\">NTCP is a physiological bile acid transporter in the plasma membrane of liver cells. NTCP is also the hepatic receptor for HBV and HDV. HBV\/HDV entry inhibitors should selectively block NTCP viral receptor function. 3D QSAR and pharmacophore models help identify novel NTCP inhibitors.<\/p><\/div>\n<p>&nbsp;<\/p>\n<p><strong>Scientific goal: <\/strong><\/p>\n<p>Development of oral and selective HBV\/HDV entry inhibitors that specifically block virus binding to NTCP, without tackling its physiological bile acid transport function. Hit compounds will be further developed into lead structures by means of molecular drug design.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>B1 Diederich\/Kolb, B3 Rahlfs\/Kolb\/van Zandbergen,\u00a0D2 Pfeiffer\/Zeuzem\/Hildt, E3 Rahlfs\/Przyborski,\u00a0E6 Schiffmann\/Laux<\/p>\n<hr \/>\n<p>References C5:<strong>1. *<\/strong>Kirstgen <em>et al. <\/em><strong>(2020) Sci Rep<\/strong> 10:21772 <strong>2.\u00a0*<\/strong>Grosser<em> et al. <\/em><strong>(2021) Front Mol Biosci <\/strong>8:689757<strong> 3.\u00a0*<\/strong>Kirstgen <em>et al. <\/em><strong>(2021) Viruses<\/strong> 13:666<strong> 4.\u00a0*<\/strong>Kirstgen <em>et al. <\/em><strong>(2021) Viruses<\/strong> 13:1489<em>.<\/em><\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> C6<\/span><span class=\"project_title\">The Fasciola kinome as source of new drug targets<\/span><br><span class=\"project_names\">Simone H\u00e4berlein<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/simone-haeberlein.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/simone-haeberlein.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>PD Dr. Simone H\u00e4berlein<\/strong><\/p><p><p>Justus-Liebig-Universit\u00e4t Gie\u00dfen<br \/>\nBFS, Institut f\u00fcr Parasitologie<br \/>\nSchubertstra\u00dfe 81<br \/>\n35392 Gie\u00dfen<br \/>\nTel.: +49 (0)641-99 38476<br \/>\nFax: +49 (0)641-99 38469<br \/>\nE-Mail:<span class=\"link-mailto\"> <a class=\"email-link\" title=\"\" href=\"mailto:Simone.Haeberlein@vetmed.uni-giessen.de\" target=\"_self\" rel=\"\">Simone.Haeberlein(at)vetmed.uni-giessen(dot)de<\/a><\/span><\/p>\n<p><a href=\"https:\/\/www.uni-giessen.de\/fbz\/fb10\/institute_klinikum\/institute\/parasitologie\/forschung\/schisto\/mitarbeiter\/haeberlein\" target=\"_blank\" rel=\"noopener\">Homepage<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description:<\/strong><\/p>\n<p>Protein kinases regulate a vast variety of cellular processes and represent promising targets not only for therapy of cancer, but also infections with parasites. One common feature of both disease types is the involvement of stem cells in tissue growth. We pursue the hypothesis that inhibition of protein kinases can be employed as a new therapeutic option against the liver fluke <em>Fasciola hepatica<\/em>, a globally prevalent zoonotic and NTD-associated pathogen. The project involves three aspects: (1) bioinformatical identification of putative drug targets within the <em>Fasciola <\/em>kinome and their genetic validation, (2) identification of kinase inhibitors with activity against liver flukes; and (3) characterization of the mode of action of potent kinase inhibitors by using biochemical and imaging-based methods.<\/p>\n<p>In cooperation with the Spengler lab (project E4) we established AP-MALDI mass spectrometry imaging to achieve \u201cdrug imaging\u201d within liver fluke tissue, which allows to study the route of drug uptake, its kinetic and tissue tropism of a drug.<\/p>\n<div id=\"attachment_549\" style=\"width: 785px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-549\" class=\"wp-image-549 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c06-grafik-01.png\" alt=\"\" width=\"775\" height=\"695\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c06-grafik-01.png 775w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c06-grafik-01-300x269.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c06-grafik-01-768x689.png 768w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/c06-grafik-01-705x632.png 705w\" sizes=\"auto, (max-width: 775px) 100vw, 775px\" \/><p id=\"caption-attachment-549\" class=\"wp-caption-text\">Strategy to identify protein kinase inhibitors as drug candidates against the liver fluke Fasciola hepatica. \u00a9Simone H\u00e4berlein<\/p><\/div>\n<p><strong>Scientific goal: <\/strong><\/p>\n<p>This projects aims to identify protein kinase inhibitors that can serve as new drug candidates for the therapy of fasciolosis.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A2 Gr\u00fcnweller lab, B4 Schlitzer lab, B5 Grevelding lab, B7 Falcone lab,\u00a0E4 Spengler lab<\/p>\n<hr \/>\n<p>References C6: <strong>1. <\/strong>Houhou <em>et al.<\/em> <strong>(2019)<\/strong> <strong><em>Sci Rep<\/em><\/strong> 9:15867. <strong>2. <\/strong>Li <em>et al.<\/em> <strong>(2019) <em>Parasitol Res<\/em><\/strong> 118(3):881-890. <strong>3.<\/strong> Morawietz <em>et al.<\/em> <strong>(2020)<\/strong> <strong><em>Front Vet Sci<\/em><\/strong> 7:611270. <strong>4. <\/strong>Mokosch <em>et al.<\/em> <strong><em>Anal Bioanal Chem<\/em><\/strong> 413(10): 2755-2766. <strong>5.<\/strong> Morawietz <em>et al.<\/em> <strong>(2022) <em>Parasitol Res<\/em><\/strong> (online ahead of print) doi: 10.1007\/s00436-021-07388-1<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":140,"menu_order":11,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-152","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - 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